This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. L-glutamine is an amino acid that is utilized in the formation of NAD, a substance that protects red blood cells from oxidative damage. Previous data showed that sickle cell anemia patients may benefit by supplementation with the amino acid, L-glutamine. Therefore, the purpose of our research is to evaluate the efficacy of this amino acid in the treatment of sickle cell anemia. This is a prospective, randomized, double blind crossover clinical trial to examine the effects of oral L-glutamine therapy on sickle cell anemia patients aged 5 years of age and older. The enrolled subjects will be randomized to either L-glutamine or placebo and will be instructed to take that assigned powder orally for 24 weeks. There will be a gradual tapering of the study medication dose for 5 weeks. Then, there will be a three-week washout period after which they will be switched to the other study medication (L-glutamine or placebo). Clinical and psychological parameters will be monitored. An independent blinded observer will follow closely the following clinical endpoints;frequency of painful crises;number of hospitalization days;level of chronic pain and amount of daily requirement for narcotics;number of work days and/or school days missed. Adverse events will also be monitored. The data obtained will be essential in understanding the role of L-glutamine in the therapy of sickle cell anemia.